OBJECTIVES: Before secretion of fetal thyroid hormone at around 16 weeks gestation normal fetal development depends on a constant supply of maternal thyroid hormone (TH), particularly thyroxine (T(4)). The detailed mechanisms of transplacental delivery of TH are still uncertain. The TH binding protein, transthyretin (TTR), is produced and secreted by placenta and may play a role in this process. The ontogeny of placental TTR is unknown. Our aim was to study changes in placental TTR in early and late pregnancy. STUDY DESIGN: We collected placentas from surgically terminated pregnancies between 6 and 17 weeks gestation (n = 44) and from normal term (38-39 weeks) pregnancies following caesarean section (n = 5). Real time-PCR, western blotting and immunohistochemistry were used to determine TTR mRNA and protein levels. RESULTS: There were highly significant correlations between gestational age and TTR mRNA (r = 0.974; p < 0.0001) and between gestational age and TTR protein (r = 0.901; p < 0.001) levels between weeks 6 and 13 of gestation. TTR expression did not increase between 13 and 17 weeks and was not different at term. Good correlation was observed between TTR mRNA and TTR protein between individual placental samples (r = 0.916; p < 0.0001). A similar trend was observed using immunohistochemical staining of placental paraffin sections. CONCLUSIONS: Our results demonstrate that TTR is expressed in the human placenta from at least 6 weeks gestation. Levels rise during the first trimester at a time when placental oxygen tensions are also rising. We hypothesise that TTR production and secretion by the placenta may facilitate transplacental delivery of TH to the fetus.